To study architecture specific but sequence non-specific DNArecognition we simulated the complex of DNA with the chromosomal protein HMG-D of Drosophila melanogaster. The proteinfunctions as a DNA chaperon facilitating DNA packing into nucleosomes [35]. We are trying to predict the unknown structureof the complex between HMG-Dand DNA. Three possible structures have been suggested by docking the NMR structure of theprotein [36] with existing structures of bent DNA. The structureswere refined in molecular dynamics simulations using the programX-PLOR [23] and one structure emerged as the most stable andconsistent with experimental observations. The structure of the sex reversal Y-factor (SRY) complexed withDNA has recently been solved [37].SRY is a sequence and architecture specific DNA binding protein belonging to the sameprotein family as HMG-D [34]. We are currently simulating theSRY-DNA complex to compare the data to HMG-Dsimulations.Thus, we will study the difference between sequence-specific and sequence-non-specific DNA recognition by proteins and mechanisms of architecture specificity. We are also working to verify our theoretical structure of the HMG-D-DNA complex using the SRY-DNA complex. The methodof homology replacement has been used to mutate SRY into HMG-D.After molecular dynamics refinement of the mutant structure we will compare it to our former predictions.